Although close to 85% of residents in long-term care facilities (LTC) have osteoporosis and the risk of osteoporotic fractures is nearly 10 times that of community dwelling elderly, few are treated and studies are scarce. The large pivotal osteoporosis trials in postmenopausal women exclude those who are sedentary, frail or functionally impaired even though this is the group at highest fracture risk. Before a fracture reduction study can be justified in this cohort, an investigation demonstrating efficacy and predictability is a necessary first step. We have previously demonstrated that zoledronic acid (ZOL) can maintain bone mineral density (BMD) and is safe in frail elderly. However a dual action anabolic antiresorptive agent has a distinct advantage to build bone rapidly. The newly approved once monthly dual action romosozumab (ROMO), provides significant improvements in BMD and fracture reduction in 1 year. If ROMO were given prior to a potent antiresorptive medication such as ZOL, this combination (rapid boost over a year with ROMO and maintain integrity 2nd year with ZOL) could provide a novel treatment paradigm in this high risk population. The concern for ROMO is the potential increase risk of cardiovascular events demonstrated in one pivotal study. Before a large fracture reduction trial can be justified in this frail population, a study demonstrating BMD efficacy and safety is imperative. We will test the hypotheses that in frail institutionalized women, one year of ROMO prior to one year of ZOL will 1) be more efficacious compared to one year of calcium plus vitamin D prior to a year of ZOL as demonstrated by improvements in conventional bone density measurements, 2) improve novel measures of bone trabecular microstructure and bone turnover markers, and 3) provide characteristics associated with responders and non-responders. To address these hypotheses, we propose to conduct a 2-year, randomized, double-blind controlled trial to test the efficacy and safety of ROMO (year 1) and ZOL (year 2) compared to calcium+vitamin D (year 1) and ZOL( year 2), in 200 institutionalized frail women age 65+ in LTC. Safety will be carefully monitored. Serious adverse events (SAE's) will be obtained by a novel electronic alert system that provides real time notifications including ROMO associated cardiovascular SAE's. This study includes innovative features: 1) focus on the neglected LTC population of frail residents in whom we have a track record of successful enrollment, 2) inclusion of a newly approved potent dual action agent feasible in LTC, 3) assessments of bone structure, 4) point of care vertebral fracture images, 5) mobile lab allowing onsite participation, and 6) electronic alerts for real time adverse events. Despite the call by national consensus groups for the past 2 decades to address osteoporosis in frail elderly, trials and treatments are sparse. This study will challenge the current paradigm of avoiding anti-osteoporosis therapy and provide an innovative approach for geriatric osteoporosis, and help target robust responders.